1.
Metabolic Regulation of the Epitranscriptome.
Thomas, JM, Batista, PJ, Meier, JL
ACS chemical biology. 2019;(3):316-324
Abstract
An emergent theme in cancer biology is that dysregulated energy metabolism may directly influence oncogenic gene expression. This is due to the fact that many enzymes involved in gene regulation use cofactors derived from primary metabolism, including acetyl-CoA, S-adenosylmethionine, and 2-ketoglutarate. While this phenomenon was first studied through the prism of histone and DNA modifications (the epigenome), recent work indicates metabolism can also impact gene regulation by disrupting the balance of RNA post-transcriptional modifications (the epitranscriptome). Here we review recent studies that explore how metabolic regulation of writers and erasers of the epitranscriptome (FTO, TET2, NAT10, MTO1, and METTL16) helps shape gene expression through three distinct mechanisms: cofactor inhibition, cofactor depletion, and writer localization. Our brief survey underscores similarities and differences between the metabolic regulation of the epigenome and epitranscriptome, and highlights fertile ground for future investigation.
2.
How do ADARs bind RNA? New protein-RNA structures illuminate substrate recognition by the RNA editing ADARs.
Thomas, JM, Beal, PA
BioEssays : news and reviews in molecular, cellular and developmental biology. 2017;(4)
-
-
Free full text
-
Abstract
Deamination of adenosine in RNA to form inosine has wide ranging consequences on RNA function including amino acid substitution to give proteins not encoded in the genome. What determines which adenosines in an mRNA are subject to this modification reaction? The answer lies in an understanding of the mechanism and substrate recognition properties of adenosine deaminases that act on RNA (ADARs). Our recent publication of X-ray crystal structures of the human ADAR2 deaminase domain bound to RNA editing substrates shed considerable light on how the catalytic domains of these enzymes bind RNA and promote adenosine deamination. Here we review in detail the deaminase domain-RNA contact surfaces and present models of how full length ADARs, bearing double stranded RNA-binding domains (dsRBDs) and deaminase domains, could process naturally occurring substrate RNAs.